Helicobacter pylori (HP infection has been identified as risk factor adenocarcinoma of the distal stomach. This cancer, which has its highest incidence in developing countries, is preceded by a sequence of histologic changes including chronic atrophic gastritis (CAG), intestinal metaplasia (IM), and dysplasia. Each step in the preneoplastic sequence increases risk for later development of malignancy. HP infection is often coincident with preneoplastic conditions but a causal association has not been proved. We hypothesize that CAG and some forms of IM indicate phenotypic but not genotypic mucosal change and that eradication of HP infection can revert gastric mucosal histology to normal epithelium. In order to evaluate this hypothesis, we intend to conduct a randomized, double-blind, placebo-control trial looking at the effect of HP eradication on gastric preneoplastic lesions. This study will be conducted in Chiapas, Mexico, a region with high rates of gastric cancer and preneoplasia. To identify subjects with CAG and/or IM, we will screen adults older than 40 years for serum pepsinogen levels. A ratio of pepsinogen I to pepsinogen II less than 5 will identify subjects to be enrolled in the endoscopy/treatment arm of the study. 300 subjects will undergo endoscopy. At endoscopy, the mucosa will be stained with methylene blue, a newly described marker for IM. Eight biopsies will be obtained and evaluated for histology and for HP infection. The subjects will then be randomized to receive two weeks of either omeprazole (20 mg BID) and amoxicillin (1 gm BID) or placebo. Six weeks following completion of the treatment, all subjects will again undergo endoscopy. Fifty subjects will also undergo a third endoscopy at the end of a year. Outcome measures will include: changes in histology (progression or reversion of Im and/or CAG), changes in IM phenotype (i.e., mucin type or Lewis antigen expression), changes in methylene blue mucosal staining and changes in pepsinogen level. We will also evaluate the value of methylene blue staining and pepsinogen testing in the identification of preneoplastic lesions. Gastric cancer is among the leading causes of cancer death worldwide. Unfortunately, studies evaluating the effect of HP eradication on gastric cancer incidence are too large and expensive to realistically undertake. Evidence that H. pylori therapy reverses preneoplastic lesions, however, could provide a foundation for gastric cancer screening and prevention trials as well as enhance understanding of preneoplasia and inflammation- related carcinogenesis.